OBJECTIVE: Diabetes mellitus (DM) is a complex, chronic disease requiring active self-management and coordinated care. This study aimed to evaluate the relationship between schizophrenia and risk of preventable, acute DM complications. RESEARCH DESIGN AND METHODS: With the use of administrative data, a retrospective study assessed acute DM complications (emergency department [ED] visits or hospitalization for hypo- or hyperglycemia and hospital admissions for infections) among Ontario residents ages 18–50 with schizophrenia and newly diagnosed DM between 1995 and 2005, comparing people with and without pre-existing schizophrenia. Primary outcome was ED visit or hospitalization for hypo- or hyperglycemia. Secondary outcome was the first of either the primary outcome or hospitalization for infection. RESULTS: People with schizophrenia had a 74% greater risk of requiring a hospital visit for hypo- or hyperglycemia (hazard ratio [HR] = 1.74, 95% confidence interval 1.42–2.12) compared with those without schizophrenia. The risk was similar when the outcome included infection (HR = 1.62, 95% CI 1.39–1.89). Outcomes remained significant after adjustment for baseline characteristics. CONCLUSIONS: People with schizophrenia are at greater risk for developing an acute complication of DM. Understanding this relationship will direct future studies assessing barriers to care and implementation of individualized approaches to care for this population.